Overtraining syndrome (OTS) represents a maladaptive response to excessive training loads and inadequate recovery periods, resulting in prolonged declines in physical performance. Both OTS as well as its and its precursor, overreaching, share molecular and physiological characteristics with chronic inflammatory conditions. Here we will focus on the effects of skeletal muscle, incorporating unpublished data from chronic inflammatory conditions to highlight how understanding these shared pathways may offer insights into therapeutic strategies aimed at mitigating both OTS and chronic inflammation. For instance, both OTS and chronic inflammation feature elevated pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β), mitochondrial dysfunction, and increased reactive oxygen species (ROS), contributing to muscle performance decline and impaired recovery. These processes mirror chronic inflammatory diseases, where NF-κB pathways leads to sustained muscle catabolism and elevated ROS levels. This suggest that OTS resembles a chronic low-grade inflammatory state, linking systemic immune dysregulation with metabolic stress of the muscle, similar to conditions like rheumatoid arthritis.